Dynamic microtubules critically regulate synaptic functions, but the role of microtubule severing in these processes is barely understood. Katanin is a neuronally expressed microtubule-severing complex regulating microtubule number and length in cell division or neurogenesis; however, its potential role in synaptic functions has remained unknown. Studying mice from both sexes, we found that katanin is abundant in neuronal dendrites and can be detected at individual excitatory spine synapses. Overexpression of a dominant-negative ATPase-deficient katanin subunit to functionally inhibit severing alters the growth of microtubules in dendrites, specifically at premature but not mature neuronal stages without affecting spine density. Notably, interference with katanin function prevented structural spine remodeling following single synapse glutamate uncaging and significantly affected the potentiation of AMPA-receptor-mediated excitatory currents after chemical induction of long-term potentiation. Furthermore, katanin inhibition reduced the invasion of microtubules into fully developed spines. Our data demonstrate that katanin-mediated microtubule severing regulates structural and functional plasticity at synaptic sites.
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http://dx.doi.org/10.1523/JNEUROSCI.0374-23.2023 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158.
The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .
View Article and Find Full Text PDFBiochem Soc Trans
January 2025
Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud-sección Medicina, Universidad de La Laguna, Tenerife, ES-38071, Spain.
Large conductance voltage- and calcium-activated potassium channels (BK channels) are extensively found throughout the central nervous system and play a crucial role in various neuronal functions. These channels are activated by a combination of cell membrane depolarisation and an increase in intracellular calcium concentration, provided by calcium sources located close to BK. In 2001, Isaacson and Murphy first demonstrated the coupling of BK channels with N-methyl-D-aspartate receptors (NMDAR) in olfactory bulb neurons.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Department of General Internal Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Background: Alzheimer's disease (AD) is an irreversible age-related neurodegenerative condition characterized by the deposition of amyloid-β (Aβ) peptides and neurofibrillary tangles. Di Huang Yi Zhi (DHYZ) formula, a traditional Chinese herbal compound comprising several prescriptions, demonstrates properties that improve cognitive abilities in clinical. Nonetheless, its molecular mechanisms on treating AD through improving neuron cells mitochondria function have not been deeply investigated.
View Article and Find Full Text PDFJ Physiol
January 2025
Department of Physiology, University College Cork, Cork, Ireland.
J Cell Mol Med
January 2025
Department of Anesthesia, Fujian Medical University Union Hospital, Fuzhou, China.
In this study, we aimed to explore the sex-specific effects and mechanisms of sevoflurane exposure on the neural development of pubertal rats on the basis of M1/M2 microglial cell polarisation and related signalling pathways. A total of 48 rat pups (24 males and 24 females) were assigned to the 0- or 2-h sevoflurane exposure group on the seventh day after birth. The Morris water maze (MWM) test was subsequently conducted on the 32nd to 38th days after birth.
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